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At least 19 recordsLinked to original sources
PubMed1989

Viability assays in organ preservation.

Assays to determine the viability of preserved organs ideally must meet two important requirements: (i) in the clinical environment, they should allow the surgeon to determine if an organ will be viable when it is transplanted (this needs to be done in a noninvasive, nondestructive manner, and currently no such assay exists), and (ii) in the research environment, they should aid in the development of improved methods of organ preservation. Currently, however, the only reliable means of assessing viability is actual transplantation. Many conventional biochemical and physiological techniques have been used to describe the mechanism of preservation-induced injury and to help improve preservation. This paper reviews some techniques that have been used to aid in the development of organ preservation.

Animals↗
PubMed1991

The role of oxygen free radicals in organ preservation.

There is controversy over the role of oxygen free radical-induced damage in preserved organs following reperfusion. Furthermore, there has been no definitive study that shows a dramatic improvement in organ functions, delayed graft functions, or improved longevity in organ transplants with oxygen free radical scavenger therapy. However, the presence of glutathione in a new organ preservation solution (University of Wisconsin, UW, solution) yields improved preservation of the liver and heart. The beneficial effect of glutathione may involve in scavenging of cytotoxic products of oxygen metabolism. The results discussed here show that glutathione improves liver preservation. Also, it is shown that glycine, and amino acid component of glutathione, can also give cytoprotection to the rabbit and dog liver tested by either isolated perfusion or orthotopic transplantation. Thus, there may be an involvement of oxygen free radicals in damage to organs hypothermically preserved and transplanted. The injury may occur within the cells or may be due to oxygen within the cells or may be due to oxygen free radicals generated in the extracellular environment.

Adenosine↗
PubMed1989

Lactobionic acid as an iron chelator: a rationale for its effectiveness as an organ preservant.

Lactobionic acid, a major constituent of a solution used to preserve organs prior to transplantation, can chelate ferric iron. This is evident by its ability to solubilize iron as well as changes that occur in the UV-VIS spectra of iron in its presence. Relative to iron (III) chelated to EDTA, the lactobionic acid-iron (III) complex is less able to participate in the Fenton reaction as measured by formaldehyde generation from DMSO and bleaching of p-N,N-dimethylnitrosoaniline. Similar effects are seen with citrate and ATP, two substances which also appear to be able to ameliorate ischemia/reperfusion injury. These findings present a rationale for the effectiveness of lactobionic acid as an organ preservant.

Catalysis↗
PubMed1992

[Organ preservation].

For organ preservation in Europe the Euro-Collins-, UW- and HTK-solution are preferred. While the HTK-solution is mainly used for heart preservation, the UW-solution has shown its advantages for longterm preservation of kidney, liver and pancreas. With regard to renal preservation the HTK-solution provides a higher buffer capacity. According to experimental and theroretical considerations the content of glucose in the Euro-Collins-solution does not seem to correspond to the current state of knowledge. In order to obtain a sufficient primary function renoprotective measurements have proven their efficacy, in addition to an optimal method of organ preservation. Especially in case of suboptimal donors the preservation time should be kept as short as possible.

Animals↗
PubMed1975

Corticosteroids in organ preservation.

1. Glucocorticoids have been empirically employed during perfusion preservation of transplantable organs. 2. Use of corticosteroids in organ preservation is based on their pharmocologic binding of released lysosomal enzymes, as membrane stabilizers, peripheral vasodilators, and inhibitors of the inflammatory response. 3. The incidence post-transplant of ATN in cadaveric kidney preservation by pulsa-tile perfusion has been reduced from 57% to 18% when the donor was protected with large doses of M-P. 4. There is sufficient clinical and laboratory evidence to substantiate the use of large doses of M-P given to the prospective donor as a protective agent against ischemic injury in organ recovery.

Glucocorticoids↗
PubMed2026

Chemoradiotherapy versus short-course radiotherapy for response-adapted organ preservation in early-stage and intermediate-stage rectal cancer (STAR-TREC): 12-month results of an international, multicentre, open-label, parallel-group, randomised, phase 2/3 trial.

BACKGROUND: Total mesorectal excision (TME) is the standard treatment for most early-stage and intermediate-stage rectal cancer but can cause substantial perioperative morbidity, functional impairment, and reduced quality of life. We assessed whether long-course chemoradiotherapy (LCCRT) or short-course radiotherapy (SCRT) could increase organ preservation and reduce surgery, toxicity, and quality-of-life harms without compromising oncological outcomes. METHODS: STAR-TREC is an international, multicentre, open-label, parallel-group, randomised, phase 2/3 trial in five European countries. Eligible patients were aged 16 years or older in the UK or aged 18 years or older elsewhere, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and rectal adenocarcinoma (≤40 mm staged as mrT1-T3bN0). In phase 2, participants were randomly assigned (1:1:1) to LCCRT-based organ preservation (LCCRT-OP; 50 Gy in 25 fractions plus oral capecitabine 825 mg/m2 twice daily), SCRT-based organ preservation (SCRT-OP; 25 Gy in five fractions), or primary TME. Phase 2 assessed feasibility, with recruitment at months 12 and 24 as the primary endpoint and feasibility thresholds of four or more and six or more randomisations per month, respectively. Phase 3 adopted a partially randomised patient-preference design, allowing participants to choose either organ preservation or TME. Participants that chose organ preservation were randomly assigned (1:1) to receive LCCRT-OP or SCRT-OP using centralised, computer-generated assignment, with stratification by country and MRI T category (≤T3a vs T3b) using minimisation. The phase 3 primary endpoint was organ-preservation 30 months after treatment initiation, defined as absence of TME, stoma, or local recurrence, which was assessed in the modified intention-to-treat population, which included participants in phase 2 and phase 3. After a planned interim analysis of unmasked phase 2 data, the trial steering committee and independent data monitoring committee recommended reporting a 12-month, modified intention-to-treat analysis of implementation outcomes for participants recruited before Aug 8, 2023. This study is registered with ISRCTN (14240288) and is closed. FINDINGS: Between June 14, 2017, and April 8, 2024, 503 participants were enrolled at 37 sites. Phase 2 enrolled 120 participants, with recruitment rates of three and six participants per month at months 12 and 24, respectively. Overall, 12-month TME-free survival was 60% (47 of 78 participants). After phase 3 recruitment ended, interim analysis of unmasked phase 2 data showed an early TME-free survival benefit with LCCRT versus SCRT (12-month median TME-free survival not reached [95% CI not reached-not reached] vs 7·6 months [95% CI 6·4-not reached]; hazard ratio [HR] 3·7 [95% CI 1·7-8·0]; posterior probability of superiority >99·5%). The trial steering committee and independent data monitoring committee therefore recommended expanded analysis of 426 participants recruited before Aug 8, 2023: 120 from phase 2 and 306 from phase 3. 17 participants withdrew before treatment, leaving 409 in the modified intention-to-treat population: 163 allocated to LCCRT, 168 to SCRT, and 78 to primary TME. 116 (28%) participants were female and 293 (72%) were male. Among participants who opted for organ preservation, 12-month TME-free survival was 78·5% (95% CI 72·4-85·1) with LCCRT and 60·6% (53·6-68·4) with SCRT (HR 1·90 [95% CI 1·29-2·81]). The most common grade 3-4 serious adverse events were gastrointestinal disorders (four [2%] with LCCRT vs six [4%] with SCRT vs six [8%] with TME) and procedural complications (three [2%] with LCCRT vs five [3%] with SCRT vs five [6%] with TME). One participant allocated to primary TME died after an anastomotic leak. INTERPRETATION: These early results support a response-adapted organ-preservation approach, with LCCRT appearing more effective than SCRT at 12 months. Organ-preservation might also reduce treatment-related toxicity compared with primary TME. Longer follow-up is needed for the prespecified 30-month endpoint and definitive functional and oncological outcomes. FUNDING: Cancer Research UK, Stand Up to Cancer, Dutch Cancer Society, Danish Cancer Society, Kom Op Tegen Kanker, Cancerfonden, ALF Region Stockholm, RCC Region Stockholm.

Humans↗
PubMed1991

Organ preservation in multimodality therapy of head and neck cancer.

Several conclusions can be drawn from the studies that have been done to evaluate induction chemotherapy and organ preservation. These principles can serve as the foundation for the design of future trials for organ preservation. 1. The addition of chemotherapy to surgery/radiation for advanced head and neck cancer has not improved overall patient survival. 2. Surgery and radiation therapy can safely and effectively be given after chemotherapy to patients who have had induction chemotherapy. 3. Neoadjuvant chemotherapy followed by definitive radiation therapy can achieve laryngeal preservation in a high percentage of patients, without compromise of survival. 4. In order to change the standard of care, organ preservation trials must be conducted in a randomized, prospective fashion. 5. Organ preservation trials must be conducted for specific sites and stages of head and neck cancer. 6. All patients with nonlaryngeal head and neck cancer who are treated with induction chemotherapy for organ preservation should be treated within a protocol setting.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

[An experimental validation of organ-preserving operations in traumatic lesions of the parenchymatous organs].

Resulting from the experiment performed on 32 dogs, the authors have established that the use of technology of tissue bioinhibition and cryogenic influence led to local cryopreservation, hypercoagulation and change in the physical properties of the damaged parenchyma. This contributes to successful performance of the organ preserving operations and prevents the development of early and long-term postoperative complications.

Animals↗
PubMed1989

[The potential for organ-preserving treatment in large uveal melanoma].

As compared with enucleation, organ-preserving treatment (photocoagulation, local excision, radiotherapy) of uveal melanoma doesn't worsen the prognosis for the patient's life. However, it was used chiefly for tumors of stages T1-T2, the prominence of the tumor not exceeding 4-5 mm. The purpose of the present communication was a study of the possibility of organ-preserving beta radiotherapy for treatment of uveal melanomas T3, the prominence of the tumor exceeding 5 mm. A new Soviet beta applicator (ruthenium-106, rhodium-106) was used for treatment of 21 patients with melanoma T3N0M0, who had refused enucleation. Average summary doses on the surface of the sclera were 1561 +/- 41 Gr. Clinical results (the follow-up period ranging from 12 to 20 months) were the following: total resorption of the tumor--3 cases; the volume of the tumor reduced by 1/2 and more--9 cases, by less than 1/2--7 cases; the size of the tumor remained unchanged--2 cases. Enucleation was made in 2 patients 3 and 4 months after radiation. The results obtained have shown beta therapy to be effective in some cases of uveal melanoma T3, this allowing to widen indications to organ-preserving treatment.

Beta Particles↗
PubMed1992

The effect of cold storage of rat thoracic aortic rings in organ preservation solutions--a study of receptor-linked vascular prostacyclin synthesis.

An important aspect of organ preservation is the maintenance of intrinsic dilator and antithrombotic mechanisms of blood vessels. Blood vessels synthesize prostacyclin (PGI2), a potent vasodilator and inhibitor of platelet adhesion and aggregation. PGI2 synthesis is controlled by complex mechanisms including adrenoceptor-linked calcium influx and protein kinase C. Since organ preservation solutions may influence these mechanisms, we investigated the effect on in vitro PGI2 synthesis of cold storage of rat aortic rings in lactobionate-raffinose solution (LRS) and hypertonic citrate kidney preservation solution (KPS) on in vitro PGI2 synthesis. Acute incubation of aortic tissue in both preservation solutions at 37 degrees C (compared with minimal essential medium) completely inhibited PGI2 synthesis when stimulated with noradrenaline (NA), phorbol ester (a protein kinase C activator), NaF (a G protein activator), or A23187. Following storage of aortic rings at 4 degrees C (for up to 72 hr) in LRS and KPS, subsequent washing and incubation in MEM, PGI2 synthesis was initially markedly enhanced in response to NA when compared with tissues stored in MEM. These enhanced responses disappeared, and PGI2 synthesis returned to normal following 1 hr incubation of tissues in MEM at 37 degrees C. These data demonstrate that cold storage in preservation fluids exerts minimal deleterious effects, not only on PGI2 synthesis, but possibly on other key processes (calcium homeostasis, protein kinase C activity) in blood vessels.

Adenosine↗
PubMed1991

Organ-preserving surgery in renal cell carcinoma--change of the therapeutical concept.

From 1976 to 1989 in 90 patients (n = 98 tumors) with renal cell carcinoma organ-preserving surgery was performed (age 25-84 years, mean 58 years). Imperative indications for organ preservation (tumor removal by partial resection with or without clamping of the artery, autotransplantation) (n = 18) were chronic renal failure, benign pathology of contralateral kidney, functional or anatomical solitary kidney, and bilateral tumors. Elective organ-preserving surgery (n = 72) was done for small peripherally located lesions and in cases of uncertain preoperative tumor dignity. Tumors removed for imperative indications were 2-11 cm (mean 6.5 cm) in size. In the elective group tumor size ranged from 1 to 6 cm (mean 3.5 cm). Follow-up was 3 months to 13 years, 1 postoperative mortality was observed in the group with imperative indication. 15/90 patients are alive without tumor, 1 patient with metastasis, 1 patient died because of metastasis and 1 for unrelated reasons. All patients beside 1 in the group with elective indication are alive without metastasis. Renal cell carcinoma has changed its clinical feature. More and more tumors are detected by ultrasound without clinical symptoms. Though radical tumor nephrectomy still is the standard operation for renal cell cancer, in cases especially with small tumors the indication for organ-preserving operation with regard to these excellent results should be given more often.

Carcinoma, Renal Cell↗
PubMed1992

[Donor allopurinol treatment improves organ preservation of the kidney also when using UW solution].

Kidney function following hypothermic preservation with Eurocollins (EC) was previously shown to be improved by donor treatment with Allopurinol (AP) [1]. The University of Wisconsin organ preservation solution (UW), however, contains Allopurinol (1 mM). A syngeneic rat kidney transplant model was used to investigate concurrent Allopurinol donor-pretreatment (40 mg/kg b.w.). Kidney graft function resulted to be improved by AP pretreatment following organ preservation with both EC or UW as evidenced by significant reduction in serum creatinine values. On day two following transplantation the respective serum creatinine values (mumol/l) with and without AP-pretreatment were 424 +/- 39 and 662 +/- 25 for EC, and 259 +/- 48 and 387 +/- 48 for UW organ preservation. Furthermore survival- and histology-data were also superior for recipients of kidney grafts from AP-pretreated donors. We conclude that Allopurinol concentration in the UW solution might be to low or that adding AP into an organ storage solution is not the best application modality.

Adenosine↗
PubMed1988

New autoperfusion preparation for long-term organ preservation.

The problems in long-term organ preservation are ischemia and toxicity from metabolic waste. A simple self-perfusing self-cleaning system has been developed that kept the heart, lungs, and kidney functioning for a mean time of 24 hours. Nine adult dogs were anesthetized and artifically ventilated. The heart and lungs were removed en bloc while being perfused by the heart. One kidney was connected to the descending aorta and inferior vena cava. No anticoagulant was used. Another group of six dogs without functioning kidneys was used as the control group. In the experimental group, urine output ranged from 26 to 48 ml/hr, aortic systolic pressures were 80-107 mm Hg, heart rate was 85-100 beats/min, serum potassium content was 3.25-4.40 mmol/l, and serum sodium content was 155-163 mmol/l. In the experimental group, blood creatinine levels decreased from 0.95 to 0.47 mg/dl during preservation; in the control group, blood creatinine levels decreased from 0.96 to 0.79 mg/dl. Lung biopsies in the preparation with the longest survival showed good preservation for as long as 24 hours, and no thrombi were present. This preparation has the advantage of no ischemic time, no foreign material in the circulation, and the ability to automatically maintain acid-base balance and blood electrolytes. The simplicity of this autoperfusion preparation may allow greater transport distance in organ procurement for subsequent transplantation.

Animals↗
PubMed1992

[Organ-preserving therapy in invasive bladder carcinoma].

With the aim of organ preservation, transurethral resection with subsequent radiotherapy (until 1985) or combined radio- and chemotherapy (since 1986) was undertaken as part of a prospective trial in 175 consecutive patients (137 men, 38 women; mean age 65 [31-90] years) with invasive bladder carcinoma, tumour stage T1-4 N0-3 M0. All patients had a transurethral resection, followed 2-6 weeks later by definitive radiotherapy at a dose of 50.4 Gy to the bladder in 28 fractions. 85 patients simultaneously with the radiotherapy received chemotherapy with cisplatin (25 mg/m2 daily) or carboplatin (65-75 mg/m2 daily) in the first and fifth weeks of radiotherapy. The 5-year survival rate for the whole group (including inoperable cases) was 50%. The survival rate as related to the T category was 53% for T1 (n = 26), 68% for T2 (n = 34), 45% for T3 (n = 94) and 22% for T4 (n = 17). 139 patients (79%) were left with a normally functioning bladder. Cystectomy was performed in 36 patients because of remaining tumour or recurrence after radiotherapy. Combined radio- and chemotherapy improved the histological remission rate, compared with an earlier control group with radiotherapy only, but it did not affect the survival rate. These data indicate that in advanced bladder carcinoma organ-preserving treatment with transurethral resection and definitive radiotherapy or combined radio- and chemotherapy can be successful.

Adult↗